Adjuvant Cemiplimab Recommended for European Approval in CSCC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion regarding the approval of adjuvant cemiplimab-rwlc (Libtayo) for the treatment of adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence after surgery and radiation. The European Commission is anticipated to make a final decision on the application in the coming months.¹

The CHMP’s opinion is informed by data from the phase 3 C-POST trial (NCT03969004). At a median follow-up of 24 months (range, 2-64), findings from the study demonstrated that patients who received adjuvant cemiplimab after surgical resection and postoperative radiotherapy (n = 209) achieved a median disease-free survival (DFS) that was not reached (95% CI, not evaluable [NE]-NE) compared with 49.4 months (95% CI, 48.5-NE) among those treated with placebo (n = 206; HR, 0.32; 95% CI, 0.20-0.51; P < .001) .² The estimated 24-month DFS rates were 87.1% (95% CI, 80.3%-91.6%) and 64.1% (95% CI, 55.9%-71.1%), respectively.

On October 8, 2025, the FDA approved cemiplimab for the adjuvant treatment of adult patients with CSCC at high risk of recurrence after surgery and radiation.³ The regulatory decision was also supported by data from C-POST.

What Were the Key Design Characteristics of C-POST?

C-POST is an ongoing, international, randomized study that enrolled adult patients with CSSC who completed curative-intent surgery with macroscopic gross resection of all disease, and postoperative radiotherapy (or concurrent chemoradiotherapy) at a biologically equivalent dose of at least 50 Gy within 2 to 10 weeks prior to random assignment.² Other key eligibility criteria included high-risk nodal or nonnodal features, an ECOG performance status at 1 or less, and adequate hepatic, renal, and bone marrow function.⁴

Initially, eligible patients were randomly assigned 1:1 to receive intravenous (IV) cemiplimab at 350 mg every 3 weeks or matching placebo.² In June 2021, the study protocol was amended to start treatment at a frequency of every 3 weeks, with a switch to every 6 weeks. Under the new protocol, IV cemiplimab administered at 350 mg every 3 weeks for 12 weeks followed by 700 mg every 6 weeks for an additional 36 weeks; patients in the placebo arm followed the same dosing schedule. The planned treatment duration was 48 weeks or until disease recurrence, unacceptable toxicity, or patient withdrawal.

The primary end point was DFS. Secondary end points included freedom from locoregional recurrence, freedom from distant recurrence, overall survival (OS), the occurrence of second primary CSCC tumors, and safety.

What Was the Safety Profile and Additional Efficacy Data?

Regarding safety, the profile of adjuvant cemiplimab in patients with CSCC at high risk of recurrence after surgery and radiation was consistent with the known safety profile of the agent in patients with advanced cancers.¹ Specifically, Any-grade adverse effects (AEs) occurred at respective rates of 91.2% and 89.2% in the investigational (n = 205) and placebo (n = 204) arms.²Any-grade serious AEs (17.6% vs 9.3%), AEs leading to treatment discontinuation (9.8% vs 1.5%), and AEs leading to death (1.0% vs 1.0%). Common any-grade AEs in both arms included fatigue (22.0% vs 21.6%), pruritus (16.1% vs 8.8%), and rash (16.1% vs 8.8%).

Further efficacy data showed that the 2-year OS rates in the investigational and control arms were 94.8% (95% CI, 89.6%-97.4%) and 92.3% (95% CI, 86.5%-95.7%). At a data cutoff of April 7, 2025, the HR for OS was 0.78 (95% CI, 0.39-1.56) in favor of the cemiplimab arm.

The estimated proportion of patients free from locoregional recurrence at 24 months was 94.6% (95% CI, 89.1%-97.3%) in the cemiplimab arm compared with 76.7% (95% CI, 69.1%-82.6%) in the placebo arm. These respective 24-month rates in terms of freedom from distant recurrence were 94.3% (95% CI, 89.0%-97.1%) and 83.8% (95% CI, 76.3%-89.0%).

References

1. Libtayo® (cemiplimab) Recommended for EU Approval by the CHMP for adjuvant treatment of cutaneous squamous cell carcinoma (CSCC) with a high risk of recurrence after surgery and radiation. News release. Regeneron. October 17, 2025. Accessed October 17, 2025. https://investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-recommended-eu-approval-chmp-adjuvant
2. Rischin D, Porceddu S, Day F, et al. Adjuvant cemiplimab or placebo in high-risk cutaneous squamous-cell carcinoma. N Engl J Med. 2025;393(8):774-785. doi:10.1056/NEJMoa2502449
3. FDA approves cemiplimab-rwlc for adjuvant treatment of cutaneous squamous cell carcinoma. FDA. October 8, 2025. Accessed October 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-adjuvant-treatment-cutaneous-squamous-cell-carcinoma
4. Study of adjuvant cemiplimab versus placebo after surgery and radiation therapy in patients with high-risk cutaneous squamous cell carcinoma. ClinicalTrials.gov. Updated